Abstract 1664: Model characterization and tumor immune profile assessment for syngeneic RM-1 murine prostate cancer in male C57BL/6 mice
Authors: Justin Snider, Derrik Germain, Patrick Allison, Alden Wong, Sylvie Kossodo
Journal: Cancer Research (2022)

Abstract Mouse syngeneic tumor models are widely used tools to demonstrate activity of novel anti-cancer immunotherapies. However, advanced prostate cancer is difficult to treat due to a lack of effective approaches for disrupting immune tolerance. RM-1 is a murine prostate cancer cell line derived from a Ras/Myc-induced prostate cancer. RM-1 is of particular interest because it is an aggressive, nonimmunogenic, potentially metastatic prostate line that is androgen independent. Subcutaneous growth kinetics were evaluated for RM-1 cells implanted at two cell inocula (1.0E+06 and 5.0E+05 cells/implant). RM-1 grew aggressively across both implant conditions, producing 100% take rate, a median tumor volume doubling time of ~2 days, and a median time to euthanasia criteria (2000 mm3) of ~11 days. Bioanalysis of tumor-infiltrating lymphocyte (TIL) composition via flow cytometry confirms that the RM-1 tumor model has characteristics of a nonimmunogenic or a “cool” tumor. CD4+ T cell and CD8+ T cell populations ranged from 0.7 to 1.9% of the CD45+ cells. Comparatively, G-MDSC and M-MDSC populations were much higher at 8.3 and 63.8% of CD45+ cells. This type of TIL profile is ideal for combination therapies, providing a clear opportunity to turn a “cool” tumor “warm” and therefore potentially more responsive to treatment. To further characterize the RM-1 model, we evaluated anti-mPD-1, anti-mPD-L1, and anti-mCTLA-4. As expected, based on the TIL profile, single agent treatment with checkpoint inhibitors produced minimal anticancer activity, with no tumor regressions, and &amp;lt;56% punitive responders. We also evaluated the anticancer activity of focal beam radiation treatment via small animal radiation research platform (SARRP). Single agent radiation treatment was highly effective, with 20, 10 and 5 Gy producing, 100, 78 and 89% incidence of putative responders. Radiation treatment at 5 Gy was selected as an ideal candidate for combination therapy. Combination therapy of radiation treatment at 5 Gy paired with anti-mPD-1, was evaluated to determine if there was an increase in activity with a two-prong approach. Historically, radiation treatment has been used to increase tumor infiltration and reduce the immunosuppressive tumor microenvironment, allowing for increased efficacy. Single agent treatment of anti-mPD-1 or radiation treatment (5 Gy) resulted in 20 and 30% incidence of putative responders. Combination therapy of anti-mPD-1 and radiation (5 Gy) resulted in 100% putative responders. Overall, the RM-1 model has proven to be a reliable and reproducible syngeneic tumor model for prostate cancer. Its presumed immunosuppressive microenvironment is clinically relevant and can provide a direct correlation to patient prostate cancer. Future studies will include orthotopic implant optimization with checkpoint inhibitor efficacy evaluation, including TIL analysis. Citation Format: Justin Snider, Derrik Germain, Patrick Allison, Alden Wong, Sylvie Kossodo. Model characterization and tumor immune profile assessment for syngeneic RM-1 murine prostate cancer in male C57BL/6 mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1664.